During mammalian gametogenesis homologous chromosomes in germline cells (precursors of sperm or eggs) pair and exchange genetic material through recombination. However, in somatic cells there is no significant chromosome pairing, and it is unclear whether and to what extent chromosomes can undergo recombination. If such chromosome recombination can be induced artificially, one can manipulate mammalian genomes in somatic cells and mimic many human diseases. For example, many cancers are caused by a rare event called loss of heterozygosity (LOH), during which the wild type copy of a particular gene is disrupted in an already heterozygous animal, resulting in a few homozygous mutant cells. Regulated chromosome recombination in somatic cells can mimic these situations.
We describe here the establishment in a mouse a system that allows us to generate site-directed chromosome recombination in somatic cells. An important added advantage of our system is the ability to label only those homozygous mutant cells in an otherwise heterozygous and hence genetically mosaic animal. Such manipulations may also be used not only to create mouse models for various human diseases, but also to study gene function in particular tissues and developmental stages, and to provide high-resolution anatomical analysis of pathology resulting from gene mutations.